الفهرس 
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Abstract
A total number of sixty apparently healthy male albino rats (150 - 170 g body weight), were obtained from Research Institute of Alexandria were used to accomplish this study. They were divided into 6 equal groups(n=10) namely Control group, Lead group (Pb), Rhodiola 200 group (R200), Rhodiola 400 group (R400), Lead + Rhodiola 200 group (Pb+R200) and Lead + Rhodiola 400 group (Pb+R400).Control group received 1ml of normal saline daily orally. Lead group was intubated with lead acetate at dose level of 25 mg/kg B.Wt orally using gastric tube. Rhodiola 200 and 400 groups were treated orally with Rhodiola extract at dose of 200 and 400 mg/kg B.Wt, respectively. Lead + Rhodiola 200 and Lead + Rhodiola 400 groups were received lead acetate and Rhodiola extract similarly as mentioned previously. All the treatments were administrated 3 times/week for 8 sucessive weeks.
Half number of the animals were sacrificed after 4 weeks from the start of the experiment and the remaining at eight week of the treatment.
Clinically, all of the groups did not show any clinical signs at any time of the experiment except nervous manifestation in lead treated group. Mortalities were recorded during the experimental period (Pb-treated 30%; Pb+R400 20%) and Pb+R200, R200 and R400-treated groups (10%, each).No mortalities were recorded in control group all over the experimental period.
Hematological findings:
All treated group did not show any significant changes in RBCs count, Hb%, PCV%, MCV, MCH and MCHC in all treatment group as compared to control group.
Four weeks post-treatment, in comparison with control group, blood platelets and total leukocytic count showed non-significant changes in different treatment group. The same results were detected at eight weeks post-treatment except for that, monocytes% was significantly decreased in R400 group.
Biochemical findings:
Serum activity of AST, ALT and ALP enzymes at four weeks post-treatment showed a significant increase in Pb-treated group only when compared to control group. Other groups did not show any significant changes compered to control group. Eight weeks post-treatment, serum activity of AST, ALT and ALP recorded a significant increase in Pb and Pb+R200-treated groups only when compared to control group, but the marked increase was recorded in Pb-treated group. Serum activity of ALT recorded a significant increase in Pb Pb+R200 and Pb+R400 treated groups when compared to control group. In the same manner, serum activity of ALP recorded a significant increase in Pb, Pb+R200 and Pb+R400 treated groups when compared to control group. But, Compering to Pb-treated group, Pb+R200 and Pb+R400-treated groups exhibited significant reduction in serum levels of ALT and ALP.
Four weeks post-treatment, in comparison with control, all different treatment groups did not recorded any significant change on serum protein profile (Total protein, albumin and globulins concentration). Eight weeks post-treatment, serum concentration of total proteins recorded a significant decrease in Pb and Pb+R200-treated groups only when compared to control group, but the greater decrease was recorded in Pb-treated group. While, serum concentration of albumin recorded a significant decrease Pb, Pb+R200 and Pb+R400- treated groups when compared to control group, but the greater increase was recorded in Pb-treated group. Serum globulin concentration showed significant reduction in Pb-treated group with no significant changes in other treated groups compared to control group.
Four weeks post-treatment, comparatively with control group, total bilirubin and indirect bilirubin recorded a significant increase in Pb, Pb+R200 and Pb+R400-treated groups by the same magnitude. Also, the level of direct bilirubin showed significant increase in Pb, Pb+R200 and Pb+R400-treated groups compared to control group, but when compared to Pb-treated group, Pb+R200 and Pb+R400-treated groups showed significant reduction. Eight weeks post-treatment, in comparison with control group, serum total bilirubin, direct and indirect bilirubin levels showed a significant increase in Pb, Pb+R200, Pb+R400-treated groups. While, these parameters were significantly decreased in groups Pb+R200 and Pb+R400 when compared to Pb-treated group.
Four weeks post-treatment, comparatively with control group, serum urea level showed a significant increase in Pb group and Pb+R200-treated group. Pb+R200 group showed a significant reduction in urea levels when compared to Pb-treated group. While, serum creatinine concentration recorded a significant increase in Pb-treated group. While other groups showed non-significant changes when compared to control group. Eight weeks post-treatment, in comparison with control group, serum urea level showed a significant increase in Pb, Pb+R200 and Pb+R400-treated group. But, the increase was greater in Pb-treated group, followed by Pb+R200 and the less was recorded in Pb+R400, serum creatinine level showed a significant increase in Pb-treated group.
Oxidative stress biomarkers:
Hepatic levels of GSH, CAT and MDA:
Four weeks post-treatment, in comparison with control group, hepatic GSH level showed a significant decrease in Pb, R200, Pb+R200 and Pb+R400 groups. Moreover, MDA level recorded a significant increase in Pb-treated group with a significant decrease in R400-treated group as compared to control group. Also, CAT activity showed a significant decrease in Pb, R200, Pb+R200 groups by the same magnitude when compared to control group. Eight weeks post-treatment, comparatively with control group, GSH level showed a significant decrease in all treated groups. Hepatic MDA level recorded a significant increase in Pb-treated group, with a significant decrease in R400-treated group as compared to control group. Additionally, hepatic CAT activity showed a significant decrease in Pb, R200, Pb+R200-treated groups by the same magnitude when compared to control group.
Renal levels of GSH, CAT and MDA:
Four weeks post-treatment, renal GSH level showed a significant decrease in Pb, R200, Pb+R200-treated groups with a significant increase in MDA level by the same magnitude, while CAT activity recorded a significant decrease in Pb-treated group only when compared to control group. Eight weeks post-treatment, in comparison with control group, renal level of GSH was significantly decreased in Pb, R200, Pb+R200 and Pb+R400 -treated groups. But, this decrease recorded its minimum value in Pb+R400 -treated group. While, renal MDA level was significantly increased in Pb, R200 and Pb+R200 -treated groups by the same magnitude when compared to control group. CAT activity in renal tissues recorded a significant decrease in Pb-treated group and a significant increase in R400-treated group as compared to control group.
Histopathological finding:
Four weeks post-treatment, liver lesions of Pb-treated group were mainly periportal ballooning degeneration and congestion of portal veins, thickening of portal area with infiltrated mononuclear inflammatory cells, focal, multifocal, or coalescing ”Patchy” coagulative hepatocytes, congested portal vein, perivascular edema, with minute mononuclear cell infiltration and fibroplasia in the portal tract. R200-treated showed nearly normal hepatic architecture with distinct hepatic cells and dilated sinusoidal spaces. R400 groups were nearly normal hepatic architecture with distinct hepatic cells and mild cellular vacuolization. However, Pb+ R200 marked moderate ballooning degeneration and focal areas of coagulative necrosis, portal infiltration of mononuclear cell, dilatation and congestion of central vein and hepatic sinusoids, nearly normal hepatocytes with mild cellular vacuolization and central congestion were noticed in Pb+R400group. Eight weeks post-treatment, Pb-treated group revealed midzonal and periportal vacuolar degeneration, focal areas of coagulative necrosis represented by nuclear pyknosis and cytoplasmic hypereosinophilia and infiltrated with mononuclear inflammatory cells. Additionally, another examined sections showed distention in the portal area, congestion of portal vein, perivascular edema and mononuclear cell infiltration, and periportal hepatocytic necrosis and vacuolization. R200-treated showed nearly normal histologic architecture, with mild vacuolar and hydropic degeneration and mild vascular and sinusoid congestion, mild mononuclear cell infiltration and kupffer cells activation were also detected in few sections. Liver tissues of rats in R400-treated group showed moderate hydropic and vacuolar degeneration of the hepatocytes and activation of Kupffer cells with no specific lesions.Pb+ R200 showed mild centrilobular hydropic degeneration and mild infiltration of mononuclear cell, moderate hydropic degeneration and thickening of portal area with infiltrated mononuclear cell was also identified. Nearly normal histologic picture of liver tissues with mild vacuolization was observed in co-treated with 400mg group.
Four weeks post-treatment, examination of kidney in Pb-treated group showed destructive lesions due to lead toxicity were concentrated in both renal tubules and the interstitial area more than the glomeruli. Cloudy swelling, vacuolar and hydropic degeneration as well as fatty changes were characteristic degenerative changes of lead toxicity in the renal epithelial cells, multifocal coagulative necrosis, minor glomerular changes were reported in the form of shrinkage and necrosis, congestion, and expanded bowman’s capsular spaces. Mild vacuolar degeneration of renal epithelium were shown in renal tissues of R200 group. Kidney from R400-treated showed nearly normal renal tissues with minimum lesions including mild cloudy swelling, hydropic degeneration, and congestion. Renal tissues Pb+R200 group revealed mild to moderate renal tubular degeneration represented by cloudy swelling and narrowed tubular lumen, and mild hydropic degeneration, minute foci of coagulative necrosis and hyaline cast formation. Mild degree of renal tubular ballooning degeneration and glomerular congestion were observed in Pb+ R400group. Eight weeks post-treatment, renal destructive changes due to lead toxicity were similar in nature to that reported in four weeks post-treatment. However, it was more prominent particularly in renal tubules and interstitium. Marked vacuolar degeneration of renal epithelium as well as few atrophied glomerulus and moderate infiltration of mononuclear inflammatory cells, attenuated glomerular epithelium and marked necrosis of renal epithelium represented by pyknotic nucleus and hyper eosinophilic cytoplasm also were noticed. Moreover, the most characteristic hallmark of the lead intoxication was eosinophilic intracytoplasmic inclusions. Renal tissues from R200 group showed mild degenerative lesions in form of mild vacuolar and hydropic degeneration, congestion. Kidney from R400-treated rats showed nearly normal kidney with minimum lesions including mild cloudy swelling, hydropic degeneration, and congestion. Mild renal degeneration in form of cloudy swelling and vacuolization were shown in Pb+R200 groups. Pb+R400groups observed mild degree of epithelial hydropic vacuolization.